DESCRIPTION (Applicant's Abstract): According to substantial evidence, an abnormal threshold for suffocation alarm underlies panic disorder. This project aims to determine whether this abnormality, as manifested in panic attacks following carbon dioxide inhalation, constitutes a trait marker for panic disorder. The following describes a high-risk paradigm to test both sensitivity and specificity. The project also seeks to refine the definitions and thresholds used to identify meaningful hypersensitivity to CO2 and to explore relationships between such hypersensitivity and morbid childhood separation anxiety. Finally, it will assess the relationship between CO2 hypersensitivity, morbid childhood separation anxiety sensitivity. It will thus work toward a synthesis of etiological theories. Never-ill subjects will be grouped by family history to yield 64 at high risk for panic disorder, 22 at high risk for affective disorder and 22 at high risk for neither disorder. Another two groups of never-ill subjects will be identified through ill probands attending an outpatient facility; 33 will have a proband with primary depression complicated by panic attacks and 22 will have a proband with panic disorder complicated by secondary depression. All high-risk subjects will undergo structured diagnostic interviews and a CO2 inhalation test. In addition, for each high-risk subject, the ill family member who defines the pedigree will be interviewed directly. According to predictions, panic attacks will occur only among subjects with a family history of autonomous panic disorder. Moreover, a relationship will emerge between hypersensitivity to CO2 inhalation and a history of morbid childhood separation anxiety. Raters will maintain annual contact with subjects using brief telephone interviews. If the study's predictions are sustained, subsequent efforts will be directed toward lengthening the follow-up period and toward an eventual, ten-year diagnostic reassessment.